A new study from the Icahn School of Medicine at Mount Sinai helps explain why some people with multiple myeloma, a type of blood cancer, stay in remission for many years after receiving CAR T cell therapy, while others see their cancer return sooner.
Published in Blood Advances , the research is the first longitudinal, single-cell, multi-omic study of cilta-cel in multiple myeloma. Cilta-cel (ciltacabtagene autoleucel) is a type of CAR T cell therapy used to treat relapsed or refractory multiple myeloma. It works by using a patient's own T cells, which are genetically engineered in a lab to target and kill cancer cells that have B cell maturation antigen (BCMA) on their surface. The modified T cells are then infused back into the patient as a one-time treatment to fight the cancer.
This study reveals that long-term remission depends on a synergy between the infused CAR T cells and the patient's own immune system, particularly the preservation of diverse T cells and the absence of suppressive myeloid cells.
"CAR T cell therapy has changed myeloma care, but not everyone maintains a long remission," said Alessandro Lagana, PhD, Assistant Professor of Oncological Sciences at the Icahn School of Medicine at Mount Sinai and senior author of the study. "We wanted to understand what's happening in the immune system of patients who stay in remission for more than five years after a single infusion."
The Mount Sinai team followed 19 patients who received cilta-cel as part of the CARTITUDE-1 clinical trial and used advanced lab tests to study their blood and bone marrow samples before and after treatment.
The study identified several immune features linked to long-term remission. Patients who stayed cancer-free for more than five years showed an early, focused expansion of CAR T cells and a broad, diverse population of healthy helper (CD4) T cells that remained active over time. In contrast, patients who relapsed sooner had higher tumor burden at baseline and an early rise in immunosuppressive myeloid cells that can blunt T cell responses.
"This research shows that long remissions depend not only on the CAR T cells we give, but also on the patient's own immune system," Dr. Lagana said. He explained that understanding these immune patterns could help doctors choose the right patients for CAR T cell therapy, watch for early signs of relapse, and develop new treatments that keep the immune system strong and responsive.
The researchers plan to test their findings in larger studies and to create a simple blood test or biomarker panel that could predict which patients are most likely to stay in remission.
The study received funding from Mount Sinai's Center of Excellence for Multiple Myeloma and included collaborations with Johnson & Johnson, which developed the CAR T cell therapy, and Immunai, which helped with data analysis.
